Serotonin’s Role in Weight Loss

A brain chemical strongly linked to mood and appetite may also directly affect fat gain, U.S. researchers reported on Tuesday.

They said levels of serotonin, the nerve-signaling chemical targeted by many antidepressants, may also direct the body to put down fat regardless of how much food is eaten.

“It may be one reason diets fail,” metabolism expert Kaveh Ashrafi of the University of California, San Francisco, who led the study, said in a telephone interview.

The findings, published in the journal Cell Metabolism, could lead to better diet drugs and treatments for diseases like diabetes.

Serotonin may help the body decide whether to burn off excess calories, or store them as fat, Ashrafi said.

He worked with roundworms for his experiment but said the findings may relate to humans. “These worms, although they are microscopic, they have around 20,000 genes … and if you compare them side by side they are about 50 percent similar to us,” he said.

Genes controlling appetite, fat storage and metabolism are especially similar, he said. The tiny worms can be manipulated to see changes to their metabolism, appetite and weight gain.

“It has been known for a long time that increasing serotonin causes fat reduction,” Ashrafi said.

“At the molecular level we are trying to understand what is the mechanism that allows that to happen. What we discovered in the worm is that those mechanisms can be separated from the mechanisms that mediate the effects of serotonin on appetite.”

The research found serotonin levels affected the worms’ appetite, but they also affected how much fat the worms accumulated, and this was via a separate process.

If the worms detect a food shortage, their metabolisms shift and they store more fat. This could explain why some people get fat more easily than others — and why dieting can cause more weight gain later.

“Different people may have similar diets, may have similar rates of physical activity, but may have very different body weights,” Ashrafi said. “Appetite is only part of it.”

But for now the remedy for excess body fat remains obvious. “Nothing in our study says that good nutrition and physical activity are not good for you,” Ashrafi said.

Simply raising serotonin levels can have serious side-effects. The diet drug fenfluramine, which has the effect of raising serotonin levels, was pulled off the market in 1997 after it caused sometimes deadly heart valve damage.